Biomedical subjects
R I Poust
Publications and source records attributed to R I Poust.
Pharmacokinetics of lithium in human plasma and erythrocytes.
The time course of lithium concentration in plasma and RBCs was measured in normal adult males following administration of single and multiple doses of lithium carbonate. From the single dose profiles, it was determined that lithium distribution between plasma and RBCs is not a simple partitioning phenomenon. The single dose time course measurements in both blood components were fit to a two compartment pharmacokinetic model in which the plasma was representative of the central compartment and the RBCs were representative of the tissue compartment. The importance of correction for trapped plasma volume in studies measuring lithium RBC kinetics was emphasized. In this study it was also demonstrated that one can accurately predict plasma and RBC lithium concentrations which are observed following multiple dosing, on the basis of single dose parameters obtained in the same subject.
Effect of chlorothiazide on the pharmacokinetics of lithium in plasma and erythrocytes.
The effect of chlorothiazide on the pharmacokinetics of lithium in both plasma and RBCs was studied in normal adult males. This was accomplished by administering single, 300 mg. doses of lithium carbonate alone and concurrently with chlorothiazide (0.5 grams/day for one week). Thiazide administration resulted in increases in plasma and RBC concentrations of 26.2 and 25.4%, respectively, as well as a 26.5% decrease in renal lithium clearance. The data were analyzed in terms of a two compartment pharmacokinetic model as previously reported (8). The results of this analysis showed that the change in renal lithium clearance could be accounted for by a 24.1% reduction in the value of ke, the excretion rate constant. It was also shown that changes in plasma lithium concentration during chronic lithium therapy would be expected to increase by 25-30% when chlorothiazide therapy is employed. The model also predicts that changes in RBC concentrations would parallel those occurring in plasma and thus no change in the RBC/plasma lithium ratio would be expected.
In vitro and in vivo transport of lithium by human erythrocytes.
An in vitro system that can be used to measure both uptake and efflux of lithium by erythrocytes (RBCs) is described. Using this system, RBC lithium accumulation in vitro was compared with in vivo RBC lithium concentrations observed in 6 normal volunteers. A significant correlation was demonstrated between in vitro RBC lithium accumulation after 48-hr incubation and in vivo RBC lithium concentration at 24, 48, 72, and 96 hr following the beginning of lithium ingestion. In addition, when efflux of lithium from RBCs in vitro was studied, a significant correlation was observed between residual lithium in RBCs and in vitro RBC lithium accumulation. Finally, it has been demonstrated that storage of blood in ice for 5 hr prior to incubation with lithium results in increased RBC lithium accumulation. A potential role for this in vitro incubation system as a model for in vivo RBC lithium accumulation is suggested.
Methodological differences in correlating digoxin dissolution with bioavailability.
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Bioequivalency of doxycycline products.
The bioavailability of three different brands and three different dosage forms of doxycycline was studied in normal subjects. Single doses, equivalent to 200 mg of doxycycline, were administered to six subjects in a crossover design as the innovator's intravenous solution given orally (Treatment A), the innovator's capsule product (Treatment B), a noninnovator's capsule product (Treatment C), the innovator's oral suspension product (Treatment D), and a second noninnovator's capsule product (Treatment E). All dosage forms contained doxycycline as the hyclate, except the suspension which contained the nonhyclate form. Serum levels were determined periodically over 48 hr, and cumulative urinary excretion was measured concurrently over a 120-hr collection period. No statistically significant differences were observed in any in vivo indicator of bioequivalence when the three capsule products were compared. Consequently, they were judged to be bioequivalent. When these capsule products were compared to the oral solution, no statistically significant differences were observed. However, when the capsules and the suspension were compared, statistically significant differences were found in the rate of absorption. In vitro dissolution tests were also conducted on the three brands of capsules, and times required to achieve 50% dissolution showed rank-order correlation with corresponding absorption rate constants.
Influence of vehicle dielectric properties on acetaminophen bioavailability from polyethylene glycol suppositories.
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Bioavailability and dissolution properties of two commercial digoxin tablets.
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Influence of repetitive dosing and altered urinary pH on doxycycline excretion in humans.
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pH-partition behavior of amino acid-like -lactam antibiotics.
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Enhanced pseudoephedrine absorption by concurrent administration of aluminum hydroxide gel in humans.
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Interaction of hexachlorophene with human epidermis. II. Comparison of kinetic and equilibrium in vivo results obtained by direct and bioelectrometric methods.
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Hexachlorophene-induced changes in electrical response specificity of human finger epidermis for sodium and potassium ions.
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Interaction of hexachlorophene with human epidermis. I. In vivo bioelectrometric study of pH influence.
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Copper-catalyzed oxidation of ascorbic acid in gels and aqueous solutions of polysorbate 80.
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Variability in the elimination of trisulfapyrimidines in man.
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